Sulfite oxidase family

Assimilatory nitrase reductases (ANR), which catalyze the reduction of nitrate to nitrite, subsequently converted to NH4 by nitrite reductase, are also members of this group [137,138]. The prototypic SO, an enzyme located in the mitochondrial intermembrane, catalyzes the biologically essential oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing methionine and cysteine amino acids. 

Amino acid sequence comparisons have shown that ANR and SO are structurally unrelated to the MFE group mentioned above. Although they are both homo-dimeric enzymes of similar molecular weights, they differ in domain organization and the number of bound cofactors. ANR is composed of three domains the N-terminal region binds the Mo-co, the central domain binds a b-type cytochrome 

In humans, genetic deficiency of SO, that can arise from either mutations in the synthetic machinery of MPT or from changes in the gene encoding SO, has dramatic consequences. These include severe neurological abnormalities, dislocated ocular lenses and mental retardation [146]. Of the four identified human mutations, two affect the active site and the others may disturb the dimer interface [140], 

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The three known crystal structures of molybdopterin-containing enzymes are from members of the first two families the aldehyde oxido-reductase from D. gigas (MOP) belongs to the xanthine oxidase family (199, 200), whereas the DMSO reductases from Rhodobacter (R.) cap-sulatus (201) and from/ , sphaeroides (202) and the formate dehydrogenase from E. coli (203) are all members of the second family of enzymes. There is a preliminary report of the X-ray structure for enzymes of the sulfite oxidase family (204). 

Molybdopterin is a component of four enzyme families all of which contain Mo(VI) the xanthine oxidase and the sulfite oxidase families with one molybdopterin and the DMSO family with two molybdopterins. There are a number of tungsten-containing enzymes with structures analogous... 

II. Sulfite oxidase family Sulfite oxidase Sulfite to sulfate... 

The assimilatory nitrate reductase (Eq. 16-61) of fungi and green plants (Chapter 24) also belongs to the sulfite oxidase family. 

The bis(l,2-enedithiolate) complexes discussed closely resemble the metal centers found in the dmso reductase family of Mo enzymes and in the tungsten enzymes. The reactivity of mono(l,2-enedithiolate) complexes remains a continuing challenge as synthetic chemists pursue accurate models for the xanthine oxidase and sulfite oxidase families of metal sites. New 1,2-dithiolate ligands [70,71] and complexes are needed to demonstrate ligand effects to help elucidation reaction mechanism. 

Members of the sulfite oxidase family involve one MPT bound to a cis-Mo02 center with an additional coordination site occupied by a cysteinyl residue. 

These studies represent the first structural analogues of the catalytic centers of members of the sulfite oxidase family in their oxidized state. 

Sulfite Oxidase Family Sulfite oxidase Chicken liver 2, 106 Mo02(SCys)(MPT) 65-heme S03 " — S04 " ISOX... 

Two other families of molybdoenzymes are the sulfite oxidase family 1 and the dimethylsulfoxide reductase family. " Nitrogenase (Chapter 24) constitutes a fourth family. Sulfife oxidase (Eq. 16-60) is an essential human liver enzyme (see also Chapter 24)... 

Kappler U, Bennett B, Rethmeier J, Schwarz G, Deutzmann R, McEwan AG, Dahl C (2000) Sulfite cytochrome c oxidoreductase from Thiobacillus novellus. Purification, characterization, and molecular biology of a heterodimeric member of sulfite oxidase family. J Biol Chem 275 13202-13212... 

FIGURE 3.16 Structural mimic of sulfite oxidase family and a functional model based on bis-dithiolene ligation. 

The nature of the catalyses effected by Mo enzymes of the xanthine oxidase and sulfite oxidase families is not yet fully established, but it is clear that they do not function in the simple, direct, manner of the DMSO reductases. ... 

Enzymes of the sulfite oxidase family coordinate a single equivalent of the pterin cofactor with an MPT-Mo 02 core in its oxidized state (54, Figure 16), and usually an additional cysteine ligand, which is provided by the polypeptide. Members of this family catalyze the transfer of an oxygen atom either to or from the substrate. Among the members of this family are sulfite oxidase, sulfite dehydrogenase, assimilatory nitrate reductases, and the YedY protein, the catalytic subunit of a sulfite oxidase homologue in E. coli So far, all members of this family contain the MPT-form of Moco without an additional dinucleotide. 

Enzymes of the sulfite oxidase family, such as human sulfite oxidase, plant nitrate reductase, or the E. coli YedY protein (sulfite oxidase homologue) bind the MPT form of Moco (54) without further modification. So far, YedY represents the only molybdoenzyme isolated from E. coli that is characterized by the presence of the MPT... 

Members of the xanthine oxidase family (i.e., the true hydroxylases) have molybdenum centers which consist of a single cofactor dithiolene ligand coordinated to a fac-MoOS-(H20) unit. Members of the sulfite oxidase family are likely to possess a single cofactor dithiolene coordinated to a cis M0O2 unit (additional coordination positions may be taken up by water and/or a cysteine residue that is conserved within the... 

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